Knowledge of the likelihood of biochemical recurrence or metastatic progression of prostate cancer is essential for rational treatment selection. In our retrospective study, with a patient population of 224 and a median follow up of 67 months, the status of ECE on MRI was a significant predictor of post-EBRT PSA relapse.
A number of clinical and pathological findings have been reported to be associated with the risk of recurrence. Despite its limited specificity for prostate cancer detection, the PSA level remains a powerful prognostic factor in the prediction of patient outcomes (25
). Similarly, high Gleason score on sextant biopsy (8
) and advanced clinical T-stage on digital rectal exam (T3a) have been associated with adverse outcomes (30
). However, because none of these clinical variables alone is sufficient to accurately predict outcome and guide treatment selection, nomograms that combine multiple variables have been developed (1
). A recent version of a nomogram for post-EBRT outcome prediction combined pre-treatment PSA, clinical T-stage, Gleason score, use (or lack) of neoadjuvant androgen deprivation therapy, and radiation dose to predict PSA-relapse in 2253 patients with a median follow-up of 7 years and achieved a concordance index of 0.72 (5
A number of studies have investigated the utility of dedicated prostate MRI findings for predicting primary prostate cancer treatment outcomes (6
). A retrospective study of 977 RP-treated men with 2-year follow-up for PSA relapse found preoperative PSA, percentage of positive prostate biopsies, endorectal MRI T-stage, biopsy Gleason score and clinical stage T2c disease to be independent predictors of PSA relapse (7
). Another study by the same group in 1025 men treated with RP showed that MRI contributed incremental prognostic value to clinical parameters in about 20% of patients, specifically those patients considered to be at intermediate risk of PSA failure based on established clinical prognostic factors; when MRI was interpreted as indicating extracapsular versus organ-confined disease in these patients, the relative risk of PSA failure was 3.6, and 5-year actuarial freedom from PSA failure was 33% versus 72% (6
Retrospective studies have shown MRI T-stage to have incremental value in predicting post-EBRT outcomes as well, though in smaller data sets (9
). In a study of 250 patients with a median follow up of 28 months, MRI findings of SVI had independent prognostic value; 4-year estimates of PSA failure-free survival for MRI SVI-negative and MRI SVI-positive patients were 68% and 33%, respectively (11
). Two recent studies by one research group showed that the predictive value of an individual MRI predictor could be influenced by other predictors in the set (9
). In the first study 80 patients had mean post-EBRT follow-up of 43 months, and clinical parameters as well as the MRI tumor stage and the radial diameter of ECE on MRI were used as predictors; the only independent predictor of metastatic relapse in multivariate analysis was the radial diameter of ECE on MRI (10
). In the second study 67 patients had mean post-EBRT follow-up of 44 months, and the volume of abnormal metabolism on MR spectroscopic imaging and multiple MRI predictors were added to the model; the only independent predictor of PSA relapse was the volume of malignant metabolism on MR spectroscopic imaging, while the independent predictors of metastatic failure were MRI tumor size and SVI on MRI (9
We found that pre-treatment PSA and ECE status on MRI were the only two significant independent predictors of PSA relapse after EBRT in the Cox model. Our results are in agreement with those of prior MRI-inclusive studies in patients treated with EBRT or RP: Although the designs of the studies varied, T3 disease on MRI was universally associated with adverse post-treatment outcomes (6
). Larger, multi-institutional trials are needed to determine whether the status of ECE on MRI (no ECE, unilateral ECE, or bilateral ECE) is consistently the strongest independent MR imaging predictor of biochemical recurrence and a direct reflection of radiocurability.
In the MR imaging TN-stage scoring system used in our study, a higher score was assigned for each increase in stage. Higher pathologic stages are associated with higher rates of biochemical recurrence (32
), and the capacity to successfully identify key features of pathologic stage (i.e., ECE, SVI and LNM) on MRI has been demonstrated (20
). In our study, stratification of patients into three groups according to MRI TN-stage () was highly predictive of biochemical recurrence of prostate cancer after radiotherapy.
As new systemic approaches are being developed to treat patients with high-risk prostate cancer, it is becoming increasingly important to distinguish the subset of patients who may benefit from these systemic treatments from those who are unlikely to benefit and who can therefore be spared from their additional toxicity. Our data could be used in the future to stratify patients into risk groups (i.e. low, intermediate, high) for different treatment options such as neoadjuvant chemotherapy, neoadjuvant hormone therapy or immunotherapy (34
The present study has several limitations, including its retrospective nature and the fact that it was performed at a single institution. MR imaging was performed with standard sequences and without a contrast agent. Diffusion-weighted imaging is now used routinely at our institution in prostate MR imaging and has been found to aid in cancer detection and assessment of tumor volume in the prostate (35
). MR spectroscopic imaging and dynamic contrast-enhanced imaging may also improve prostate cancer detection and staging, particularly for less experienced readers (18
). However, in 2000, when the MR images used in this study began to be collected, such advanced MR imaging techniques were not part of our routine imaging protocols.
Another possible limitation of our study is the relatively wide range of the intervals between MR imaging and the start of EBRT (6-415 days). However, the median interval was only 85 days. The longer interval time periods between MRI and initiation of EBRT reflect in general patients who were treated with neoadjuvant androgen deprivation therapy (ADT) where prostate volume reduction was required prior to the initiation of radiotherapy. In some cases maximal volume reduction was only achieved after 9-10 months before the radiotherapy was initiated. It should also be noted that the two radiologists who retrospectively interpreted the MR images for our study had experience reading prostate MR imaging at an institution where it is routinely performed. Therefore, the results may only represent the performance of this technique at institutions where prostate MRI is used routinely and will need to be validated in other academic and community settings.
At present, prostate MRI is a technically and interpretatively challenging modality used primarily at academic centers, and thus its nationwide use for prostate cancer prognostication cannot be recommended. To date, all MRI-inclusive studies on outcome prediction in patients with prostate cancer have been retrospective and have been based on small sample sizes. Yet even if a prospective multi-institutional MRI prediction study is initiated, it will probably require a minimum of a decade to complete. We believe that the presently available evidence warrants the use of MRI findings to identify high-risk patients at centers where prostate MRI is routinely performed. Among patients with MRI evidence of extraprostatic disease, particularly bilateral ECE and/or SVI, more intensive treatment regimens may be warranted to achieve superior disease control outcomes. These regimens could include longer courses of androgen deprivation therapy, as well as more intensive dose escalation regimens which can be achieved with the combination of brachytherapy and IMRT.